CA2009008A1 - Process for the preparation of substituted cyclopropanecarbaldehydes - Google Patents
Process for the preparation of substituted cyclopropanecarbaldehydesInfo
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- CA2009008A1 CA2009008A1 CA002009008A CA2009008A CA2009008A1 CA 2009008 A1 CA2009008 A1 CA 2009008A1 CA 002009008 A CA002009008 A CA 002009008A CA 2009008 A CA2009008 A CA 2009008A CA 2009008 A1 CA2009008 A1 CA 2009008A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/04—Saturated ethers
- C07C43/12—Saturated ethers containing halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C325/00—Thioaldehydes; Thioketones; Thioquinones; Oxides thereof
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/20—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
PS/5-17442/=
Process for the preparation of substituted cyclopropanecarbaldehydes Abstract The invention relates to a process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form a bisulfite adduct of formula
Process for the preparation of substituted cyclopropanecarbaldehydes Abstract The invention relates to a process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form a bisulfite adduct of formula
Description
090~)8 PS/5-17442/=
Process for the preparation of substituted cyclopropanecarbaldehydes The invention relates to a novel process for the synthesis of 1-alkylthio- and l-benzyl-thio-substituted cyclopropanecarbaldehydes of formula R~-S ~CHO
~ (I) in which R1 is C1-C4alkyl or benzyl.
The cyclopropanecarbaldehydes of formula I are valuable intermediates for the synthesis of agrocbemical active substances. They are valuable, for example, for the preparation of the cycloalkanecarbaldoxime carbamates known from DE-A-21 20 908 and for the synthesis of the 2-acyl-cyclohexane- 1,3-diones having herbicidal and plant growth-regulating activity described in EP-A-O 243 313.
-Those cyclohexanediones are substituted inter alia in position S by a 1-aLtcylthio- or a l-benzylthio-cycloprop-1-yl radical. They may be prepared by a malonic ester synthesis starting from l-alkylthio- or 1-benzylthio-cyclopropanecarboxaldehydes, respectively. In that process, first of all the aldehyde is condensed with acetone to forrn the corresponding 4-(1-alkyl-(or benzyl-)thio)-cyclopropyl-but-3-en-2-one which is subsequently cyclised to form the cyclohexanedione using malonic ester or cyanoacetic acid ester. The cyclo-hexanedione obtainable in this manner is then functionalised in position 2 in a manner known ~ se.
A process for the preparation of compounds of formula I in which Rl is C1-C4aIkyl is known from DE-A-2 120 908. In that five-step process, chloroacetonitrile is reacted by way of alkylthioacetonitrile to form a l-alkylthiocyclopropanecarbonitrile. Thatcompound is then hydrolysed, converted first into the acid chloride and tben into an amide, and reduced to the aldehyde by means of LiAlH4.
This process has numerous disadvantages. Apart from the poor total yield of the process, 20(390~)8 complex process steps are necessary for the individllal stages of the reaction. Moreover, the alkylthioacetonitrile required as starting compound is corrosive and irritating to the eyes.
In contrast to that process, the invention relates to a process for the preparation of cyclopropanecarbaldehydes of formula Rl-S CHO
2~ (I) in which Rl is Cl-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula ~ 'R2 (Il) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4- trihalobutyl ether of formula X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by C1-C4aLkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, Cl-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form a bisulf~lte adduct of formula 3 Z0(~90C1~3 OH
X-CH2-CH2 CHX-lH-So/3 y0 (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, and c) then cyclising the adduct, in the presence of a base, with a thiolate of formula .~
Rl-S~3 Z~ (V) in which Rl is Cl-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
Process steps a), b) and c) are novel. The invention relates to the combination of all three process steps, as described hereinbefore, to the combination of the process steps a) + b), and b) + c), and to the individual steps a), b) and c) on their own.
The 1,2,4-trihalobutyl ethers of formula III and the bisulfite adducts of forrnula IV are also novel and the present invention relates to those also.
The invention thus relates to the novel 1,2,4-trihalobutyl ethers of formula j~
X-CHzCH2-CHX-C~ (m) in which X is halogen and R2 is unsubstituted or halo-substituted C1-ClOaLkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4aLkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aLkyl, C1-C4alkoxy, nitro or cyano, and to the novel bisulfite adducts of formula OH
X-CHzCH2-CHX-CH-S03e y~E\ (IV) xoo~o~)~
Process for the preparation of substituted cyclopropanecarbaldehydes The invention relates to a novel process for the synthesis of 1-alkylthio- and l-benzyl-thio-substituted cyclopropanecarbaldehydes of formula R~-S ~CHO
~ (I) in which R1 is C1-C4alkyl or benzyl.
The cyclopropanecarbaldehydes of formula I are valuable intermediates for the synthesis of agrocbemical active substances. They are valuable, for example, for the preparation of the cycloalkanecarbaldoxime carbamates known from DE-A-21 20 908 and for the synthesis of the 2-acyl-cyclohexane- 1,3-diones having herbicidal and plant growth-regulating activity described in EP-A-O 243 313.
-Those cyclohexanediones are substituted inter alia in position S by a 1-aLtcylthio- or a l-benzylthio-cycloprop-1-yl radical. They may be prepared by a malonic ester synthesis starting from l-alkylthio- or 1-benzylthio-cyclopropanecarboxaldehydes, respectively. In that process, first of all the aldehyde is condensed with acetone to forrn the corresponding 4-(1-alkyl-(or benzyl-)thio)-cyclopropyl-but-3-en-2-one which is subsequently cyclised to form the cyclohexanedione using malonic ester or cyanoacetic acid ester. The cyclo-hexanedione obtainable in this manner is then functionalised in position 2 in a manner known ~ se.
A process for the preparation of compounds of formula I in which Rl is C1-C4aIkyl is known from DE-A-2 120 908. In that five-step process, chloroacetonitrile is reacted by way of alkylthioacetonitrile to form a l-alkylthiocyclopropanecarbonitrile. Thatcompound is then hydrolysed, converted first into the acid chloride and tben into an amide, and reduced to the aldehyde by means of LiAlH4.
This process has numerous disadvantages. Apart from the poor total yield of the process, 20(390~)8 complex process steps are necessary for the individllal stages of the reaction. Moreover, the alkylthioacetonitrile required as starting compound is corrosive and irritating to the eyes.
In contrast to that process, the invention relates to a process for the preparation of cyclopropanecarbaldehydes of formula Rl-S CHO
2~ (I) in which Rl is Cl-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula ~ 'R2 (Il) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4- trihalobutyl ether of formula X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by C1-C4aLkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, Cl-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form a bisulf~lte adduct of formula 3 Z0(~90C1~3 OH
X-CH2-CH2 CHX-lH-So/3 y0 (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, and c) then cyclising the adduct, in the presence of a base, with a thiolate of formula .~
Rl-S~3 Z~ (V) in which Rl is Cl-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
Process steps a), b) and c) are novel. The invention relates to the combination of all three process steps, as described hereinbefore, to the combination of the process steps a) + b), and b) + c), and to the individual steps a), b) and c) on their own.
The 1,2,4-trihalobutyl ethers of formula III and the bisulfite adducts of forrnula IV are also novel and the present invention relates to those also.
The invention thus relates to the novel 1,2,4-trihalobutyl ethers of formula j~
X-CHzCH2-CHX-C~ (m) in which X is halogen and R2 is unsubstituted or halo-substituted C1-ClOaLkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4aLkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aLkyl, C1-C4alkoxy, nitro or cyano, and to the novel bisulfite adducts of formula OH
X-CHzCH2-CHX-CH-S03e y~E\ (IV) xoo~o~)~
in which X is halogen nnd Y is n cation equivalent of an alkall metal or alkaline earth metal ion.
The tetrahydrofurans of formula II are valuable starting compounds for the process according to the invention. Some of these compounds are known from the literature. The compounds of formula II can be prepared analogously to processes known from the litera-ture. The alcoholysis of 2,3-dihalotetrahydrofurans [M. Holik et al.; (Chem. Zvesti; 25 (1971), 9); V. Zezula and M. Kratochvil; Collect. Czech. Chem. Commun.; 35 (1970), 1745], [L.M. Bolotina et aL; Khim. Geterotsikl. Soedin; 4 (1968), 200], for example, pro-vides a convenient route to this class of compounds. The Zn- or ZnCI2-catalysed addition of oxiranes to 2,3-dichlorotetrahydrofuran or mixtures of 2,3- dichlorotetrahydrofuran with tetrahydrofuran is another convenient method of producing 2-[2- or 4-chloroalkyl-substituted]-3-chlorotetrahydrofurans of formula II [M. Kratochvil, Collect. Czech. Chem.
Commun. 25 (1960),1353].
The invention also relates to the novel tetrahydrofurans of formula II
, x -R2 (II) o in which X is halogen and R2 is unsubsdtuted or hal~substituted Cl-CIOalkyl, C3-C6-cycloaL1cyl that is unsubstituted or substituted by halogen, Cl-C4aIkyl or by Cl-C4aLtcoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aL~cyl, Cl-C4aLlcoxy, nitro or cyano, with the proviso that when X is chlorine R2 is not unsub-stituted Cl-C6aLIcyl, cyclohexyl, C4-CIOalkyl substituted in the 2 position by chlorine, or 4-chlorobutyl, and that when X is bromine or iodine R2 is not Cl-C4alkyl.
The individual Process Steps of the invention, and combinations thereof, are defined as follows:
Two-step processes:
, .
The process for the preparation of cyclopropanecarbaldehydes of forrnula Z0~90~)8 Rl-S CHO
(I) in which R1 is C1-C4alkyl or benzyl, which comprises b) reacting a 1,2,4-trihalobutyl ether of formula ,,', ~
X-CH2-CH2-CHX-C~ (III) :~ in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or subsdtuted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubsdtuted or substituted by halogen, C1-C4alkyl, Cl-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution to form a bisulfite adduct of formula , OH
X-CH2-CH2-CHX-CH-S03 Y~ (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion and c) subsequently cyclising the adduct, in the presence of a base, with a thiolate of formula R~-Se z~ (V) in which Rl is Cl-C4aLtcyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I;
and the process for the preparation of a bisulfite adduct of formula OH
X-CH2-CH2-CHX-CH-So3e y~ (IV) 20~0~)8 in which X is halogen ancl Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises a) reacting a tetrahydrofuran of formula x in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4- trihalobutyl ether of formula X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-CIOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form the bisulfite adduct of formula IV.
Single-step processes:
The process for the preparation of 1,2,4-trihalobutyl ethers of formula X-CH2-CH2-CHX-C~ (III) 2~S9 in which X is halogen and R2 is unsubstituted or halo-substituted C~-C~Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, which comprises a) reacting a tetrahydrofuran of forrnula x o in which X is halogen and R2 is unsubstituted or halo-substituted Cl-CIOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by C~-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with a halogenating agent;
the process for the preparation of a bisulfite adduct of formula OH
X-CH2-CH2-CHX-CH-S03 Y~3 (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises b) reacting a 1 ,2,4-trihalobutyl ether of formula /x X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution;
20(~
and the process for the preparatioll of cyclopropanecarbaldehydes of formula R I -S CHO
2~ (I) in which Rl is Cl-C4alkyl or benzyl, which comprises c) cyclising a bisulflte adduct of formula OH
X-CH2-CH2-CHX-CH-So3 y~ (IV) in which X is halogen and Y is a cation equivalent of an aLIcali metal or aLkaline earth metal ion, in the presence of a base, with a thiolate of formula Rl-Se Z~3 (V) in which Rl is Cl-C4alkyl or benzyl and Z is a cation equivalent of an aLkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
In the definitions used in this description, the generic terms used have especially the following individual meanings:
Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, or an isomeric pentyl, hexyl, heptyl, octyl, nonyl or decyl radical. Where R2 is alkyl, Cl-C4-alkyl is preferred.
Halogen is fluorine, chlorine, bromine or iodine, especially chlorine or bromine.
Alkali metal and alkaline earth metal ions are especially lithium, sodium, potassium and also the divalent ions of magnesium and calcium. In the case of the bisulfite adducts the sodium and potassium salts are preferred, with the sodium salts being more especially preferred.
Haloalkyl as a meaning of the substituent R2 is especially 2-chloroethyl, 2-chloropropyl, 2()0~ )8 2-chlorobutyl or 4-chlorobutyl.
Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopentyl or cyclohexyl. The cycloalkyl radicals may in turn be substituted by halogen, alkyl or alkoxy. Preferably, the cycloalkyl radicals are unsubstituted or are substituted by up to three identical or different substituents from halogen, Cl-C4alkyl and C~-C4alkoxy.
R2 as phenyl or benzyl is preferably unsubstituted, but can also be substituted by up to three identical or different substituents from halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro and cyano. R2 as alkyl is preferably unsubstituted Cl-C4alkyl.
In the case of the two-step or the three-step process (combinadon of Process Steps b) + c);
a) + b); or a) + b) + c)) the syntheses may advantageously be carried out as "one-pot processes", that is to say without isolation of the respective intermediates.
The following features have proved advantageous for the individual Process Steps:
Process SteP a) The halogenation of the tetrahydrofuran II is carried out successfully in the presence of from 0.005 to 0.5 mol of a catalyst, optionally with from 0.0001 to 0.5 mol of a proton donor, from 1 to 6 mol of the halogenating agent and from 0 to 200 ml of an inert solvent per mol of educt. Suitable proton donors are, for example, water, alcohols, acids, such as hydrochloric acid, sulfuric acid, carboxylic acids and sulfonic acids, and ammonium ions (with the exception of quaternary ammonium ions). Preferred proton donors are water, alcohols and hydrochloric acid. In an especially advantageous manner, Process Step a) is carried out without a solvent in the presence of from 0.02 to 0.1 mol of a catalyst, optio-nally with from 0.001 to 0.01 mol of water, and from 1.10 to 1.15 mol of halogenating agent.
Especially prefe~red are those halogenating agents of which the residues can be removed from the reaction mixture easily owing to their ready volatility, such as, for example, thionyl chloride or thionyl bromide. Thionyl chloride is particularly suitable.
There may be mentioned as catalysts especially aromatic amines, such as pyridine, lutidine, 4-dimethylaminopyridine, quinoline, picoline, tertiary amines, such as N,N-dimethylaniline, 4-N',N'-dimethylaminopyridine or 1,4-diazabicyclo[2.2.2]octane, and - In 20~0~8 also trialkylamines, such as triethylamine or ethyldiisopropylamine, or amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorus triamide.
Suitable solvents are, inter alia, aromatic hydrocarbons, such as toluene, xylene or benzene; ethers, such as tetrahydrofuran, dioxane, diethyl ether or diisopropyl ether;
alicyclic or aliphatic hydrocarbons, such as cyclohexane, hexane or higher-boiling aL~canes; chlorinated hydrocarbons, such as dichloromethane or trichloromethane.
The process is preferably carried out at temperatures of from room temperature to approximately 140C, especially in a range of from 30 to 100C and more especially from 80 to 85C.
In an especially preferred form, the process is carried out at the boiling temperature of the reaction mixture in the presence of from 0.02 to 0.1 mol of pyridine or triethylamine as catalyst, from 1.10 to 1.15 mol of thionyl chloride, and without a solvent. In this advantageous form of Process Step a), the product obtained is a 1,4-dichloro-2-halobutyl ether of formula Cl-CH2-CH2-CHX-CH (IIIa~
in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloaLkyl that is unsubstituted or substituted by halogen, Cl-C4aLkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aL~yl, C1-C4alkoxy, nitro or cyano.
Process SteP b) The hydrolysis of the ether III to form the bisulfite adduct IV is advantageously carried out in an aqueous two-phase system under controlled pH conditions. When using a 40 %
sodium bisulfite solution, in particular the following preferred and especially preferred ratios of solvents and educts come into consideration:
Preferred are from 1.0 to 2.0 mol of sodium bisulfite (in the form of a 40 % aqueous solution), from 20 to 200 ml of water and from 20 to 200 ml of an inert organic solvent per mol of ether III. Especially preferred are from 1.0 to 1.1 mol of sodium bisulfite (in 2C~ 0~8 the form of a 40 % aqueolls sollltion), from 40 to 60 ml of water and from 40 to 60 ml of organic solvent per mol of ether III.
The reaction is advantageously carried out at temperatures of from 0 to 100C, and preferably at temperatures of from 30 to 80C.
The pH value of the reaction mixture is maintained in a range of approximately from 2 tO 7, preferably from 3.0 to 3.5, by the controlled addition of a base. NaOH or KOH (for example in the form of a 30 % aqueous solution) are suitable as bases.
Preferably, an ether of formula IIIa is used for carrying out Process Step b).
The solvents suitable for Process Step b) correspond to those mentioned in Step a). In addition, esters such as, for example, ethyl acetate, are suitable. Toluene is especially preferred.
The bisulfite adduct obtainable by Process Step b) can be obtained in a simple manner by first of all gently heating the reaction mixture and removing the organic phase at that elevated temperature. The product IV crystallises from the aqueous phase in a high degree of purity and can either be separated off, or directly further processed in Process Step c) in the form of an aqueous suspension.
Process Step c) The bisulfite adduct IV is suspended in from 400 to 1000 ml, preferably from 600 to 800 ml, of water per mol of educt, or the suspension obtainable in accordance with Process Step b) is used directly. At temperatures of from -20 to +40C, preferably from 0 to 5C, from 1.0 to 1.5 mol, preferably from 1.0 to 1.05 mol, of thiolate V are added thereto. The reaction mixture is adjusted to a basic pH value with from 1.02 to 2.20 mol, preferably from 1.02 to 2.0 mol, of sodium hydroxide solution. The product can then be extracted from the reaction mixture.
For carrying out Process Step c), bisulfite adducts of formula OH
Cl-CH2-CH2-CHX-CH-S03e Y~\ (IVa) 2(~90()8 in which X is hnlogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion are especially preferred.
Preferred thiolates are the sodiun1 and potassium thiolates of formula V.
Apart from sodium hydroxide solution, other alkali metal and alkaline earth metal hydroxides or carbonates may be used as bases in the afore-mentioned Reaction Steps b) and c).
The process according to the invention is distinguished by numerous advantages as compared with that known from the prior art. It uses readily available educts and reagents. Carrying out the reaction is uncomplicated ttemperature, solvents, pH control, the use of water as reaction medium, isolation of the products, good removal of the by-products and residues etc.). The process can be carried out with or without isolation of the intermediates. The bisulfite adduct IV is stable in storage. In addition, the process has a high yield and high product quality in every single reaction step.
The following Examples illustrate the invention.
PreParatory Examples P.1. Preparation of (1.2.4-tlichlorobut-1-vl)-methyl ether 130.9 g (1.1 mol) of thionyl chloride are added dropwise at from 80 to 85C, over a period of 2 hours, to 136.5 g (1.0 mol) of 3-chloro-2-methoxytetrahydrofuran and 1.58 g (0.02 mol) of pyridine, evolution of gas occurring immediately. The reaction mixture is further stirred until the evolution of gas has ceased, and is then cooled to room temperature.
185.7 g (97 %) of the title compound of formula C~ 7 CH2-CH2-fH-CH-O-CH3 Cl are isolated in the form of a light-brown liquid (Comp. No~ 1.01).
Z~ 90~)8 Spectroscopic data for compound No. 1.01:
H-NMR (90 MHz, CDCI3):
ppm Identification 1.9 - 2.9 multiplet 2H-C(3) 3.4 - 4.0 multiplet 2H-C(4) 3.63 singlet H3C-O
4.1-4.6 multiplet H-C(2) 4.68 and 4.76 2 doublets, ratio 1:2, J = 7 and J = 4 H-C(l) MS: 157(10), 155(16),121(2),119(7),107(3), 105(10), 94(2),92(5),81(34),79(100), 55(3),53(5),51(13); M = 191.5; (for both diastereoisomers).
The compounds of Table I can be prepared analogously (using SOCl2 or SOBr2 as halo-genating agent). J
Table I
Compounds of formula ~c"' X'-cH2-cH2-CHX -CH-OR2 (III) Comp. No. X' X' X" R2 B.p./pressure Yield 1.01 Cl Cl Cl CH3 + 100C/5.3 Pa 97 %
1.02 Br Cl Br CH3 1.03 Br Br Br CH3 1.04 Cl Br Cl CH3 + 85C/2.7 Pa 96.8 %
1.05 Cl Cl Cl C2Hs 1.06 Br Cl Br C2Hs 1.07 Br Br Br C2Hs 1.08 Cl Rr Cl C2Hs 14~ Z0(~ )8 P.2. Preparatiotl of the bisul~lte ~Iddu~cts IV
P. 2.1. Preparation of the bisulfite adduct of 2.4-dichlorobutYraldehvde 185.6 g (0.97 mol) of (1,2,4-trichlorobut-l-yl)-methyl ether are added dropwise at from 40 to 45C, over a period of one hour, tO 310.0 g (1.0 mol) of a 33.5 % aqueous sodium hydrogen sulfite solution and 50 ml of toluene. At the same time the pH value is main-tained at from 3.0 to 3.5 with 30 % aqueous NaOH solution. The reaction mixture is then heated to from 70 to 75 and the toluene phase is removed and discarded. The product crystallises out on cooling the aqueous phase to 15C.
162.1 g (66 %) of the title compound of formula OH
Cl-CH2-CH2-CHCI-CH-S03~3 Naffl are isolated in the form of a colourless powder (Comp. No. 2.01).
By recrystallisation of the mother liquors it is possible to isolate a further 58.2 g (23.7 %) of the title compound.
P. 2.2. Preparation of the bisulfite adduct of 2,4-dichlorobutvraldehyde from 3-chloro-2-methoxYtetrahvdrofuran (In P. 2.2.1. Usin~ triethYlamine as catalvst 13.1 g (110 mmol) are added dropwise at from 80 to 85C, over a period of 2 hours, to 13.6 g (100 mmol) of 3-chloro-2-methoxytetrahydrofuran and 0.2 g (2 mmol) of triethyl-amine. The (1,2,4-trichlorobut-1-yl)-methyl ether obtainable in this manner is added over a period of 30 minutes at from 40 to 45C to 31.0 g (100 mrnol) of a 33.5 % aqueous sodium hydrogen sulfite solution and 6 ml of toluene, the pH value of the reaction mixture being held at from 3.0 to 3.5 with 30 % NaOH solution. The reaction mixture is then heated to from 70 to 75C, the toluene phase is removed and the aqueous phase is cooled to room temperature, the product precipitating.
Z(;~9()~8 ; ~ ` 68.3 g (94.8 %) of the title compound of formula ;.
Cl-CH2-CH2-CHCI-CH.S03~3 Na~
, are isolated in the form of a 34 % aqueous suspension (Comp. No. 2.01).
P. 2.2.2. Usin~ lutidine as catalvst Analogously to Example P. 2.2.1., 66.1 g (91.7 %) of the dtle compound of formula OH
Cl-CH2-CH2-CHCI-CH-S03~3 Na~
~' in the forrn of a 34 % aqueous bisulfite adduct suspension (Comp. No. 2.01) are obtained from 13.6 g (100 mmol) of 3-chloro-2-methoxytetrahydrofuran, 0.1 g (2 mmol) of lutidine and 13.1 g (110 mmol) of thionyl chloride,31.0 g (100 mmol) of 33.5 % aqueous sodium bisulfite solution and 6 ml of toluene.
lH-NMR (360 MHz, D20): ~ = 2.1 - 2.45 and 2.5 - 2.65 (2m, 2H-C(3; 3.7 - 3.95 (m, 2H-C(4)); 4.55 - 4.9 (3 complex signals, H-C(1) and H-C(2)).
, ; The compounds of Table II are obtained analogously to the P.2. Preparatory Examples.
Table II
Compounds of formula X" OH
X'-CH2-CH2~H--CH-So3~3 Na~
'5 ~, ' Z~090~8 Comp. No. X X" ¦ Yleld [%]
2.01 Cl Cl 95 2.02 Br Cl 2.03 Br Br 2.04 Cl Br 90 1) 1) from 3-bromo-2-methoxytetrahydrofuran with SOC12 as halogenating agent and pyridine as catalyst.
P. 3. Preparation of the cyclopropanecarbaldehvdes I
,, P. 3.1. I-methylthiocvclopropanecarbaldehyde 42.8 g (175 mmol) of 2,4-dichlorobutyraldehyde bisulfite adduct (suspended in 200 ml of water) are added dropwise at from 0 to 5C, over a period of one hour, to 98.5 g(225 mmol) of a 16 % aqueous sodium methyl thiolate solution and 60.0 g (450 mmol) of a 30 % aqueous sodium hydroxide solution. The mixture is stirred for a further 45 minutes and then 100 ml of dichloromethane are added and the aqueous phase is separated off.
The organic phase is concentrated by evaporation in vacuo (50C/S00 mbar~ in a rotary evaporator.
1~.4 g (95.6 %) of the title compound of formula CH3-S ~CHO
(Compound No. 4.01) are isolated.
The compounds of Table III are isolated in an analogous manner.
20~0~)8 Table III
Example Educt RIS~Na~E) Product Yield . .
P.3.1.2. srcH2-cH2cHcl~Hso3Na CH3SNa 2~
~3t IOH CH3-S CHO
P.3.1.3. ClCH2CH2CH-CHSO3Na CH3SNa 2~ 90 %
sr OH
CH3-S ~CHO
P.3.1.4. srcH2cH2cH cHso3Na CH3SNa 2~
F ~' CH3(CH2)3-S ~CHO
P.3.1.5. ClCH2CH2CH-CHSO3Na CH3(CH2)3SNa ~ 69 %
Cl OH C6H5-CH2-S CHO
P.3.1.6. clcH2cHlH-cHso3Na C6Hs-CH2SNa 2~ 58 %
P. 3.2. l-methylthiocvclopropanecarbaldehyde from 3-chloro-2-methoxytetrahYdrofuran without isolation of the intermediates 273.0 g (2.0 mol) of 3-chloro-2-methoxytetrahydrofuran, 3.16 g (40 mmol) of pyridine, 261.8 g (2.2 mol) of thionyl chloride, 620 g (2.0 mol) of 33.5 % of aqueous sodium hydrogen sulfite solution and 100 ml of toluene are reacted analogously to ~xample P.2.2.
to form an aqueous suspension of the 2,4-dichlorobutyraldehyde bisulfite adduct. The aqueous suspension obtainable in this manner is diluted with 210 ml of water and cooled to 0C. 876.3 g (2.0 mol~ of a 16 % sodium methyl thiolate solution and 533.0 g (4.0 mol) of a 30 % aqueous sodium hydroxide solution are then added dropwise over a period of 3 hours at from 0 to 5C. The mixture is then stirred for a further 45 minutes at from 0 to 5C, heated to room temperature, extracted with toluene or dichloromethane. the aqueous phase is separated off and the organic phase is concentrated in vacuo in a rotary evaporator.
- 18- X0~90~)8 185.7 g (80 %) of the ~itle compoulld of formula CH3-S ~CHO
(Comp. No. 4.01) are isolated.
The compounds of Table IV can be prepared analogously to the above Preparatory Examples:
Table IV
Compounds of fonnula Rl-S CHO
(I) Comp. No. Rl Boilingpoint/pressure Yield 4.01 CH3 + 91 to +92C/10000 Pa 80 %
4.02 CH3(CH2)3- 61%
4.03 C6H5-CH2- +90 to +91Cl1.3 Pa51 %
4.04 C2Hs +57 to +58C/1800 Pa 4.05 . C3H7-n +74 to +76C/2000 Pa 4.06 C3H7-i +67 to +68C/2000 Pa
The tetrahydrofurans of formula II are valuable starting compounds for the process according to the invention. Some of these compounds are known from the literature. The compounds of formula II can be prepared analogously to processes known from the litera-ture. The alcoholysis of 2,3-dihalotetrahydrofurans [M. Holik et al.; (Chem. Zvesti; 25 (1971), 9); V. Zezula and M. Kratochvil; Collect. Czech. Chem. Commun.; 35 (1970), 1745], [L.M. Bolotina et aL; Khim. Geterotsikl. Soedin; 4 (1968), 200], for example, pro-vides a convenient route to this class of compounds. The Zn- or ZnCI2-catalysed addition of oxiranes to 2,3-dichlorotetrahydrofuran or mixtures of 2,3- dichlorotetrahydrofuran with tetrahydrofuran is another convenient method of producing 2-[2- or 4-chloroalkyl-substituted]-3-chlorotetrahydrofurans of formula II [M. Kratochvil, Collect. Czech. Chem.
Commun. 25 (1960),1353].
The invention also relates to the novel tetrahydrofurans of formula II
, x -R2 (II) o in which X is halogen and R2 is unsubsdtuted or hal~substituted Cl-CIOalkyl, C3-C6-cycloaL1cyl that is unsubstituted or substituted by halogen, Cl-C4aIkyl or by Cl-C4aLtcoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aL~cyl, Cl-C4aLlcoxy, nitro or cyano, with the proviso that when X is chlorine R2 is not unsub-stituted Cl-C6aLIcyl, cyclohexyl, C4-CIOalkyl substituted in the 2 position by chlorine, or 4-chlorobutyl, and that when X is bromine or iodine R2 is not Cl-C4alkyl.
The individual Process Steps of the invention, and combinations thereof, are defined as follows:
Two-step processes:
, .
The process for the preparation of cyclopropanecarbaldehydes of forrnula Z0~90~)8 Rl-S CHO
(I) in which R1 is C1-C4alkyl or benzyl, which comprises b) reacting a 1,2,4-trihalobutyl ether of formula ,,', ~
X-CH2-CH2-CHX-C~ (III) :~ in which X is halogen and R2 is unsubstituted or halo-substituted Cl-C1Oalkyl, C3-C6-cycloalkyl that is unsubstituted or subsdtuted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubsdtuted or substituted by halogen, C1-C4alkyl, Cl-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution to form a bisulfite adduct of formula , OH
X-CH2-CH2-CHX-CH-S03 Y~ (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion and c) subsequently cyclising the adduct, in the presence of a base, with a thiolate of formula R~-Se z~ (V) in which Rl is Cl-C4aLtcyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I;
and the process for the preparation of a bisulfite adduct of formula OH
X-CH2-CH2-CHX-CH-So3e y~ (IV) 20~0~)8 in which X is halogen ancl Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises a) reacting a tetrahydrofuran of formula x in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4- trihalobutyl ether of formula X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-CIOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form the bisulfite adduct of formula IV.
Single-step processes:
The process for the preparation of 1,2,4-trihalobutyl ethers of formula X-CH2-CH2-CHX-C~ (III) 2~S9 in which X is halogen and R2 is unsubstituted or halo-substituted C~-C~Oalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, which comprises a) reacting a tetrahydrofuran of forrnula x o in which X is halogen and R2 is unsubstituted or halo-substituted Cl-CIOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by C~-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with a halogenating agent;
the process for the preparation of a bisulfite adduct of formula OH
X-CH2-CH2-CHX-CH-S03 Y~3 (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises b) reacting a 1 ,2,4-trihalobutyl ether of formula /x X-CH2-CH2-CHX-C~ (III) in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, Cl-C4alkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution;
20(~
and the process for the preparatioll of cyclopropanecarbaldehydes of formula R I -S CHO
2~ (I) in which Rl is Cl-C4alkyl or benzyl, which comprises c) cyclising a bisulflte adduct of formula OH
X-CH2-CH2-CHX-CH-So3 y~ (IV) in which X is halogen and Y is a cation equivalent of an aLIcali metal or aLkaline earth metal ion, in the presence of a base, with a thiolate of formula Rl-Se Z~3 (V) in which Rl is Cl-C4alkyl or benzyl and Z is a cation equivalent of an aLkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
In the definitions used in this description, the generic terms used have especially the following individual meanings:
Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, or an isomeric pentyl, hexyl, heptyl, octyl, nonyl or decyl radical. Where R2 is alkyl, Cl-C4-alkyl is preferred.
Halogen is fluorine, chlorine, bromine or iodine, especially chlorine or bromine.
Alkali metal and alkaline earth metal ions are especially lithium, sodium, potassium and also the divalent ions of magnesium and calcium. In the case of the bisulfite adducts the sodium and potassium salts are preferred, with the sodium salts being more especially preferred.
Haloalkyl as a meaning of the substituent R2 is especially 2-chloroethyl, 2-chloropropyl, 2()0~ )8 2-chlorobutyl or 4-chlorobutyl.
Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopentyl or cyclohexyl. The cycloalkyl radicals may in turn be substituted by halogen, alkyl or alkoxy. Preferably, the cycloalkyl radicals are unsubstituted or are substituted by up to three identical or different substituents from halogen, Cl-C4alkyl and C~-C4alkoxy.
R2 as phenyl or benzyl is preferably unsubstituted, but can also be substituted by up to three identical or different substituents from halogen, Cl-C4alkyl, Cl-C4alkoxy, nitro and cyano. R2 as alkyl is preferably unsubstituted Cl-C4alkyl.
In the case of the two-step or the three-step process (combinadon of Process Steps b) + c);
a) + b); or a) + b) + c)) the syntheses may advantageously be carried out as "one-pot processes", that is to say without isolation of the respective intermediates.
The following features have proved advantageous for the individual Process Steps:
Process SteP a) The halogenation of the tetrahydrofuran II is carried out successfully in the presence of from 0.005 to 0.5 mol of a catalyst, optionally with from 0.0001 to 0.5 mol of a proton donor, from 1 to 6 mol of the halogenating agent and from 0 to 200 ml of an inert solvent per mol of educt. Suitable proton donors are, for example, water, alcohols, acids, such as hydrochloric acid, sulfuric acid, carboxylic acids and sulfonic acids, and ammonium ions (with the exception of quaternary ammonium ions). Preferred proton donors are water, alcohols and hydrochloric acid. In an especially advantageous manner, Process Step a) is carried out without a solvent in the presence of from 0.02 to 0.1 mol of a catalyst, optio-nally with from 0.001 to 0.01 mol of water, and from 1.10 to 1.15 mol of halogenating agent.
Especially prefe~red are those halogenating agents of which the residues can be removed from the reaction mixture easily owing to their ready volatility, such as, for example, thionyl chloride or thionyl bromide. Thionyl chloride is particularly suitable.
There may be mentioned as catalysts especially aromatic amines, such as pyridine, lutidine, 4-dimethylaminopyridine, quinoline, picoline, tertiary amines, such as N,N-dimethylaniline, 4-N',N'-dimethylaminopyridine or 1,4-diazabicyclo[2.2.2]octane, and - In 20~0~8 also trialkylamines, such as triethylamine or ethyldiisopropylamine, or amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorus triamide.
Suitable solvents are, inter alia, aromatic hydrocarbons, such as toluene, xylene or benzene; ethers, such as tetrahydrofuran, dioxane, diethyl ether or diisopropyl ether;
alicyclic or aliphatic hydrocarbons, such as cyclohexane, hexane or higher-boiling aL~canes; chlorinated hydrocarbons, such as dichloromethane or trichloromethane.
The process is preferably carried out at temperatures of from room temperature to approximately 140C, especially in a range of from 30 to 100C and more especially from 80 to 85C.
In an especially preferred form, the process is carried out at the boiling temperature of the reaction mixture in the presence of from 0.02 to 0.1 mol of pyridine or triethylamine as catalyst, from 1.10 to 1.15 mol of thionyl chloride, and without a solvent. In this advantageous form of Process Step a), the product obtained is a 1,4-dichloro-2-halobutyl ether of formula Cl-CH2-CH2-CHX-CH (IIIa~
in which X is halogen and R2 is unsubstituted or halo-substituted Cl-ClOalkyl, C3-C6-cycloaLkyl that is unsubstituted or substituted by halogen, Cl-C4aLkyl or by Cl-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, Cl-C4aL~yl, C1-C4alkoxy, nitro or cyano.
Process SteP b) The hydrolysis of the ether III to form the bisulfite adduct IV is advantageously carried out in an aqueous two-phase system under controlled pH conditions. When using a 40 %
sodium bisulfite solution, in particular the following preferred and especially preferred ratios of solvents and educts come into consideration:
Preferred are from 1.0 to 2.0 mol of sodium bisulfite (in the form of a 40 % aqueous solution), from 20 to 200 ml of water and from 20 to 200 ml of an inert organic solvent per mol of ether III. Especially preferred are from 1.0 to 1.1 mol of sodium bisulfite (in 2C~ 0~8 the form of a 40 % aqueolls sollltion), from 40 to 60 ml of water and from 40 to 60 ml of organic solvent per mol of ether III.
The reaction is advantageously carried out at temperatures of from 0 to 100C, and preferably at temperatures of from 30 to 80C.
The pH value of the reaction mixture is maintained in a range of approximately from 2 tO 7, preferably from 3.0 to 3.5, by the controlled addition of a base. NaOH or KOH (for example in the form of a 30 % aqueous solution) are suitable as bases.
Preferably, an ether of formula IIIa is used for carrying out Process Step b).
The solvents suitable for Process Step b) correspond to those mentioned in Step a). In addition, esters such as, for example, ethyl acetate, are suitable. Toluene is especially preferred.
The bisulfite adduct obtainable by Process Step b) can be obtained in a simple manner by first of all gently heating the reaction mixture and removing the organic phase at that elevated temperature. The product IV crystallises from the aqueous phase in a high degree of purity and can either be separated off, or directly further processed in Process Step c) in the form of an aqueous suspension.
Process Step c) The bisulfite adduct IV is suspended in from 400 to 1000 ml, preferably from 600 to 800 ml, of water per mol of educt, or the suspension obtainable in accordance with Process Step b) is used directly. At temperatures of from -20 to +40C, preferably from 0 to 5C, from 1.0 to 1.5 mol, preferably from 1.0 to 1.05 mol, of thiolate V are added thereto. The reaction mixture is adjusted to a basic pH value with from 1.02 to 2.20 mol, preferably from 1.02 to 2.0 mol, of sodium hydroxide solution. The product can then be extracted from the reaction mixture.
For carrying out Process Step c), bisulfite adducts of formula OH
Cl-CH2-CH2-CHX-CH-S03e Y~\ (IVa) 2(~90()8 in which X is hnlogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion are especially preferred.
Preferred thiolates are the sodiun1 and potassium thiolates of formula V.
Apart from sodium hydroxide solution, other alkali metal and alkaline earth metal hydroxides or carbonates may be used as bases in the afore-mentioned Reaction Steps b) and c).
The process according to the invention is distinguished by numerous advantages as compared with that known from the prior art. It uses readily available educts and reagents. Carrying out the reaction is uncomplicated ttemperature, solvents, pH control, the use of water as reaction medium, isolation of the products, good removal of the by-products and residues etc.). The process can be carried out with or without isolation of the intermediates. The bisulfite adduct IV is stable in storage. In addition, the process has a high yield and high product quality in every single reaction step.
The following Examples illustrate the invention.
PreParatory Examples P.1. Preparation of (1.2.4-tlichlorobut-1-vl)-methyl ether 130.9 g (1.1 mol) of thionyl chloride are added dropwise at from 80 to 85C, over a period of 2 hours, to 136.5 g (1.0 mol) of 3-chloro-2-methoxytetrahydrofuran and 1.58 g (0.02 mol) of pyridine, evolution of gas occurring immediately. The reaction mixture is further stirred until the evolution of gas has ceased, and is then cooled to room temperature.
185.7 g (97 %) of the title compound of formula C~ 7 CH2-CH2-fH-CH-O-CH3 Cl are isolated in the form of a light-brown liquid (Comp. No~ 1.01).
Z~ 90~)8 Spectroscopic data for compound No. 1.01:
H-NMR (90 MHz, CDCI3):
ppm Identification 1.9 - 2.9 multiplet 2H-C(3) 3.4 - 4.0 multiplet 2H-C(4) 3.63 singlet H3C-O
4.1-4.6 multiplet H-C(2) 4.68 and 4.76 2 doublets, ratio 1:2, J = 7 and J = 4 H-C(l) MS: 157(10), 155(16),121(2),119(7),107(3), 105(10), 94(2),92(5),81(34),79(100), 55(3),53(5),51(13); M = 191.5; (for both diastereoisomers).
The compounds of Table I can be prepared analogously (using SOCl2 or SOBr2 as halo-genating agent). J
Table I
Compounds of formula ~c"' X'-cH2-cH2-CHX -CH-OR2 (III) Comp. No. X' X' X" R2 B.p./pressure Yield 1.01 Cl Cl Cl CH3 + 100C/5.3 Pa 97 %
1.02 Br Cl Br CH3 1.03 Br Br Br CH3 1.04 Cl Br Cl CH3 + 85C/2.7 Pa 96.8 %
1.05 Cl Cl Cl C2Hs 1.06 Br Cl Br C2Hs 1.07 Br Br Br C2Hs 1.08 Cl Rr Cl C2Hs 14~ Z0(~ )8 P.2. Preparatiotl of the bisul~lte ~Iddu~cts IV
P. 2.1. Preparation of the bisulfite adduct of 2.4-dichlorobutYraldehvde 185.6 g (0.97 mol) of (1,2,4-trichlorobut-l-yl)-methyl ether are added dropwise at from 40 to 45C, over a period of one hour, tO 310.0 g (1.0 mol) of a 33.5 % aqueous sodium hydrogen sulfite solution and 50 ml of toluene. At the same time the pH value is main-tained at from 3.0 to 3.5 with 30 % aqueous NaOH solution. The reaction mixture is then heated to from 70 to 75 and the toluene phase is removed and discarded. The product crystallises out on cooling the aqueous phase to 15C.
162.1 g (66 %) of the title compound of formula OH
Cl-CH2-CH2-CHCI-CH-S03~3 Naffl are isolated in the form of a colourless powder (Comp. No. 2.01).
By recrystallisation of the mother liquors it is possible to isolate a further 58.2 g (23.7 %) of the title compound.
P. 2.2. Preparation of the bisulfite adduct of 2,4-dichlorobutvraldehyde from 3-chloro-2-methoxYtetrahvdrofuran (In P. 2.2.1. Usin~ triethYlamine as catalvst 13.1 g (110 mmol) are added dropwise at from 80 to 85C, over a period of 2 hours, to 13.6 g (100 mmol) of 3-chloro-2-methoxytetrahydrofuran and 0.2 g (2 mmol) of triethyl-amine. The (1,2,4-trichlorobut-1-yl)-methyl ether obtainable in this manner is added over a period of 30 minutes at from 40 to 45C to 31.0 g (100 mrnol) of a 33.5 % aqueous sodium hydrogen sulfite solution and 6 ml of toluene, the pH value of the reaction mixture being held at from 3.0 to 3.5 with 30 % NaOH solution. The reaction mixture is then heated to from 70 to 75C, the toluene phase is removed and the aqueous phase is cooled to room temperature, the product precipitating.
Z(;~9()~8 ; ~ ` 68.3 g (94.8 %) of the title compound of formula ;.
Cl-CH2-CH2-CHCI-CH.S03~3 Na~
, are isolated in the form of a 34 % aqueous suspension (Comp. No. 2.01).
P. 2.2.2. Usin~ lutidine as catalvst Analogously to Example P. 2.2.1., 66.1 g (91.7 %) of the dtle compound of formula OH
Cl-CH2-CH2-CHCI-CH-S03~3 Na~
~' in the forrn of a 34 % aqueous bisulfite adduct suspension (Comp. No. 2.01) are obtained from 13.6 g (100 mmol) of 3-chloro-2-methoxytetrahydrofuran, 0.1 g (2 mmol) of lutidine and 13.1 g (110 mmol) of thionyl chloride,31.0 g (100 mmol) of 33.5 % aqueous sodium bisulfite solution and 6 ml of toluene.
lH-NMR (360 MHz, D20): ~ = 2.1 - 2.45 and 2.5 - 2.65 (2m, 2H-C(3; 3.7 - 3.95 (m, 2H-C(4)); 4.55 - 4.9 (3 complex signals, H-C(1) and H-C(2)).
, ; The compounds of Table II are obtained analogously to the P.2. Preparatory Examples.
Table II
Compounds of formula X" OH
X'-CH2-CH2~H--CH-So3~3 Na~
'5 ~, ' Z~090~8 Comp. No. X X" ¦ Yleld [%]
2.01 Cl Cl 95 2.02 Br Cl 2.03 Br Br 2.04 Cl Br 90 1) 1) from 3-bromo-2-methoxytetrahydrofuran with SOC12 as halogenating agent and pyridine as catalyst.
P. 3. Preparation of the cyclopropanecarbaldehvdes I
,, P. 3.1. I-methylthiocvclopropanecarbaldehyde 42.8 g (175 mmol) of 2,4-dichlorobutyraldehyde bisulfite adduct (suspended in 200 ml of water) are added dropwise at from 0 to 5C, over a period of one hour, to 98.5 g(225 mmol) of a 16 % aqueous sodium methyl thiolate solution and 60.0 g (450 mmol) of a 30 % aqueous sodium hydroxide solution. The mixture is stirred for a further 45 minutes and then 100 ml of dichloromethane are added and the aqueous phase is separated off.
The organic phase is concentrated by evaporation in vacuo (50C/S00 mbar~ in a rotary evaporator.
1~.4 g (95.6 %) of the title compound of formula CH3-S ~CHO
(Compound No. 4.01) are isolated.
The compounds of Table III are isolated in an analogous manner.
20~0~)8 Table III
Example Educt RIS~Na~E) Product Yield . .
P.3.1.2. srcH2-cH2cHcl~Hso3Na CH3SNa 2~
~3t IOH CH3-S CHO
P.3.1.3. ClCH2CH2CH-CHSO3Na CH3SNa 2~ 90 %
sr OH
CH3-S ~CHO
P.3.1.4. srcH2cH2cH cHso3Na CH3SNa 2~
F ~' CH3(CH2)3-S ~CHO
P.3.1.5. ClCH2CH2CH-CHSO3Na CH3(CH2)3SNa ~ 69 %
Cl OH C6H5-CH2-S CHO
P.3.1.6. clcH2cHlH-cHso3Na C6Hs-CH2SNa 2~ 58 %
P. 3.2. l-methylthiocvclopropanecarbaldehyde from 3-chloro-2-methoxytetrahYdrofuran without isolation of the intermediates 273.0 g (2.0 mol) of 3-chloro-2-methoxytetrahydrofuran, 3.16 g (40 mmol) of pyridine, 261.8 g (2.2 mol) of thionyl chloride, 620 g (2.0 mol) of 33.5 % of aqueous sodium hydrogen sulfite solution and 100 ml of toluene are reacted analogously to ~xample P.2.2.
to form an aqueous suspension of the 2,4-dichlorobutyraldehyde bisulfite adduct. The aqueous suspension obtainable in this manner is diluted with 210 ml of water and cooled to 0C. 876.3 g (2.0 mol~ of a 16 % sodium methyl thiolate solution and 533.0 g (4.0 mol) of a 30 % aqueous sodium hydroxide solution are then added dropwise over a period of 3 hours at from 0 to 5C. The mixture is then stirred for a further 45 minutes at from 0 to 5C, heated to room temperature, extracted with toluene or dichloromethane. the aqueous phase is separated off and the organic phase is concentrated in vacuo in a rotary evaporator.
- 18- X0~90~)8 185.7 g (80 %) of the ~itle compoulld of formula CH3-S ~CHO
(Comp. No. 4.01) are isolated.
The compounds of Table IV can be prepared analogously to the above Preparatory Examples:
Table IV
Compounds of fonnula Rl-S CHO
(I) Comp. No. Rl Boilingpoint/pressure Yield 4.01 CH3 + 91 to +92C/10000 Pa 80 %
4.02 CH3(CH2)3- 61%
4.03 C6H5-CH2- +90 to +91Cl1.3 Pa51 %
4.04 C2Hs +57 to +58C/1800 Pa 4.05 . C3H7-n +74 to +76C/2000 Pa 4.06 C3H7-i +67 to +68C/2000 Pa
Claims (13)
1. A process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form a bisulfite adduct of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, and c) then cyclising the adduct, in the presence of a base, with a thiolate of formula (V) in which R1 is C1-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
2. A process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with thionyl chloride to form a 1,4-dichloro-2-halobutyl ether of formula (IIIa) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula IIIa with an aqueous bisulfite solution to form a bisulfite adduct of formula (IVa) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, and c) then cyclising the adduct, in the presence of a base, with a thiolate of formula (V) in which R1 is C1-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
3. A process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises b) reacting a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution to form a bisulfite adduct of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion and c) subsequently cyclising the adduct, in the presence of a base, with a thiol ate of formula (V) in which R1 is C1-C4 alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
4. A process according to claim 3 which comprises b) reacting a 1,4-dichloro-2-halobutyl ether of formula (IIIa) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution to form a bisulfite adduct of formula (IVa) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion and c) subsequently cyclising the adduct, in the presence of a base, with a thiolate of formula (V) in which R1 is C1-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
5. A process for the preparation of a bisulfite adduct of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent to form a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, and b) then reacting the compound of formula III with an aqueous bisulfite solution to form the bisulfite adduct of formula IV.
6. A process for the preparation of 1,2,4-trihalobutyl ethers of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10aLkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, which comprises a) reacting a tetrahydrofuran of formula (II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with a halogenating agent.
7. A process for the preparation of a bisulfite adduct of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, which comprises b) reacting a 1,2,4-trihalobutyl ether of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with an aqueous bisulfite solution.
8. A process for the preparation of cyclopropanecarbaldehydes of formula (I) in which R1 is C1-C4alkyl or benzyl, which comprises c) cyclising a bisulfite adduct of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion, in the presence of a base, with a thiolate of formula (V) in which R1 is C1-C4alkyl or benzyl and Z is a cation equivalent of an alkali metal or alkaline earth metal ion, to form a cyclopropanecarbaldehyde of formula I.
9. 1,2,4-trihalobutyl ethers of formula (III) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano.
10. 1,4-dichloro-2-halobutyl ethers of formula (IIIa) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano.
11. Bisulfite adducts of formula (IV) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion.
12. Bisulfite adducts of formula (IVa) in which X is halogen and Y is a cation equivalent of an alkali metal or alkaline earth metal ion.
13. Compounds of formula II
(II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with the proviso that when X is chlorine R2 is not unsubsti-tuted C1-C6alkyl, cyclohexyl, C4-C10alkyl substituted in the 2-position by chlorine, or 4-chlorobutyl, and that when X is bromine or iodine R2 is not C1-C4alkyl.
(II) in which X is halogen and R2 is unsubstituted or halo-substituted C1-C10alkyl, C3-C6-cycloalkyl that is unsubstituted or substituted by halogen, C1-C4alkyl or by C1-C4alkoxy, or phenyl or benzyl each of which is unsubstituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy, nitro or cyano, with the proviso that when X is chlorine R2 is not unsubsti-tuted C1-C6alkyl, cyclohexyl, C4-C10alkyl substituted in the 2-position by chlorine, or 4-chlorobutyl, and that when X is bromine or iodine R2 is not C1-C4alkyl.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH36589 | 1989-02-02 | ||
| CH365/89-9 | 1989-02-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2009008A1 true CA2009008A1 (en) | 1990-08-02 |
Family
ID=4185369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002009008A Abandoned CA2009008A1 (en) | 1989-02-02 | 1990-01-31 | Process for the preparation of substituted cyclopropanecarbaldehydes |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4968836A (en) |
| EP (1) | EP0381623B1 (en) |
| JP (1) | JPH0637415B2 (en) |
| KR (1) | KR900012900A (en) |
| AT (1) | ATE87617T1 (en) |
| BR (1) | BR9000447A (en) |
| CA (1) | CA2009008A1 (en) |
| DE (1) | DE59001086D1 (en) |
| DK (1) | DK0381623T3 (en) |
| ES (1) | ES2054313T3 (en) |
| GR (1) | GR3007854T3 (en) |
| IL (1) | IL93228A (en) |
| ZA (1) | ZA90757B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2055394T3 (en) * | 1989-02-02 | 1994-08-16 | Ciba Geigy Ag | PROCEDURE FOR THE OBTAINING OF 1-ALKYLTIO- AND 1-BENCILTIO-1-FORMILCICLOPROPANES. |
| US5189227A (en) * | 1989-02-02 | 1993-02-23 | Ciba-Geigy Corporation | 1,2,4-trihalobutyl ethers |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3239560A (en) * | 1962-03-05 | 1966-03-08 | Procter & Gamble | Method for preparation of halide hydroxysulfonate |
| US3721711A (en) * | 1970-04-29 | 1973-03-20 | Exxon Research Engineering Co | Cycloalkane carboxaldoxime carbamates |
| EP0243313B1 (en) * | 1986-04-24 | 1990-05-16 | Ciba-Geigy Ag | Acyl-cyclohexane diones and their oxime ethers exhibiting a herbicidal and plant growth activity |
-
1990
- 1990-01-24 ES ES90810057T patent/ES2054313T3/en not_active Expired - Lifetime
- 1990-01-24 EP EP90810057A patent/EP0381623B1/en not_active Expired - Lifetime
- 1990-01-24 AT AT90810057T patent/ATE87617T1/en not_active IP Right Cessation
- 1990-01-24 DK DK90810057.1T patent/DK0381623T3/en not_active Application Discontinuation
- 1990-01-24 DE DE9090810057T patent/DE59001086D1/en not_active Expired - Fee Related
- 1990-01-30 US US07/472,677 patent/US4968836A/en not_active Expired - Fee Related
- 1990-01-31 IL IL9322890A patent/IL93228A/en not_active IP Right Cessation
- 1990-01-31 CA CA002009008A patent/CA2009008A1/en not_active Abandoned
- 1990-02-01 KR KR1019900001162A patent/KR900012900A/en not_active Application Discontinuation
- 1990-02-01 ZA ZA90757A patent/ZA90757B/en unknown
- 1990-02-01 BR BR909000447A patent/BR9000447A/en not_active Application Discontinuation
- 1990-02-02 JP JP2024275A patent/JPH0637415B2/en not_active Expired - Lifetime
-
1993
- 1993-05-14 GR GR920403070T patent/GR3007854T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL93228A (en) | 1995-01-24 |
| EP0381623B1 (en) | 1993-03-31 |
| DK0381623T3 (en) | 1993-08-02 |
| JPH0637415B2 (en) | 1994-05-18 |
| IL93228A0 (en) | 1990-11-05 |
| GR3007854T3 (en) | 1993-08-31 |
| KR900012900A (en) | 1990-09-03 |
| JPH02240038A (en) | 1990-09-25 |
| ES2054313T3 (en) | 1994-08-01 |
| ZA90757B (en) | 1990-10-31 |
| EP0381623A1 (en) | 1990-08-08 |
| DE59001086D1 (en) | 1993-05-06 |
| US4968836A (en) | 1990-11-06 |
| BR9000447A (en) | 1991-01-15 |
| ATE87617T1 (en) | 1993-04-15 |
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